DESCRIPTION (Applicant's abstract): The long-term objective of this grant is to advance understanding of the etiologic role of obstetric complications (OCs), and their relation to brain and neuropsychological abnormalities in bipolar disorder. If OCs are indeed etiologically significant, it could have important health implications, as optimal obstetric care targeted on individuals at high risk for bipolar disorder would then offer an attractive approach to primary prevention of the disorder. The specific aims are to investigate whether it is possible (a) not only to replicate recent study findings of a significant excess of OCs in patients with bipolar disorder, compared with either normal controls or the patients' own siblings, but also (b) to pioneer investigation of whether, in bipolar patients, OCs may be associated with brain abnormalities seen on MRI (magnetic resonance imaging) scans and with poor performance on neuropsychological tests. The research design and methods involve obtaining OC data on the births and pregnancies of (a) 40 first-admission patient probands with bipolar disorder aged 18-50 and (b) 40 psychiatrically normal control probands similar in age, gender, ethnicity, and handedness, along with (c) approximately 120 of the bipolar and control probands' respective siblings. Diagnoses will use DSM-IV criteria, based on structured diagnostic interviews (SCID), supplemented by chart review. Summary OC scores will be obtained by applying published rating scales to OC data obtained from interviews with subjects' mothers. OC, diagnostic, MRI, and neuropsychological assessments will be made blindly with respect to each other. The proposed study is highly cost-effective, as it will "piggyback" collection of OC data onto a larger study already funded to collect diagnostic, MRI and neuropsychological test data on bipolar and control probands. Statistics appropriate to obtained OC data distributions will be used to test the hypotheses that bipolar probands have higher (i.e., worse) OC scores than either normal controls or the bipolar probands' own siblings, and that higher OC scores will be associated (a) with structural brain abnormalities observed on MRI scans and (b) with poorer neuropsychological test performance.